Synthesis, Molecular Docking and Cytotoxicity Evaluation of 2-(4-Substituted-Benzyl) Isoindoline-1, 3-Dione Derivatives as Anticancer Agents

Alireza Aliabadi; Alireza Foroumadi; Maliheh Safavi; Sussan Kabudanian Ardestani

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Synthesis, Molecular Docking and Cytotoxicity Evaluation of 2-(4-Substituted-Benzyl) Isoindoline-1, 3-Dione Derivatives as Anticancer Agents

Author(s):

Alireza Aliabadi^1,*,

Alireza Foroumadi²,

Maliheh Safavi³,

Sussan Kabudanian Ardestani³

1Department of Medicinal Chemistry, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran

2Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14174, Iran

3Institute of Biochemistry and Biophysics, Department of Biochemistry, University of Tehran, Tehran, Iran

Journal of Reports in Pharmaceutical Sciences:Vol. 1, issue 1; 23-26

Published online:Mar 20, 2012

Article type:Research Article

Received:Feb 17, 2012

Accepted:Mar 10, 2012

How to Cite:Alireza AliabadiAlireza ForoumadiMaliheh SafaviSussan Kabudanian ArdestaniSynthesis, Molecular Docking and Cytotoxicity Evaluation of 2-(4-Substituted-Benzyl) Isoindoline-1, 3-Dione Derivatives as Anticancer Agents.J Rep Pharm Sci.1(1):e147800.

Abstract

The development and discovery of new anticancer agents is one of the main goals in medicinal chemistry. The conventional anticancer drugs are concomitant with high incidence of unpleasant side effects like severe gastrointestinal side effects and bone marrow suppression. In recent years, various selective anticancer agents have been emerged like dasatinib. The exact mechanism of dasatinib is the inhibition of c-Src tyrosine kinase. In fact, over-expression of some types of tyrosine kinases such as c-Src have been proved in some neoplastic disorders like breast cancer. As mentioned above, unwanted side effects and also the emergence of resistant tumors are encouraging agents for discovery of new anticancer drugs. Synthesis and in vitro cytotoxicity evaluation of 2-(4-Substituted-benzyl) isoindoline-1,3-dione derivatives (3-7) in T47D breast cancer cell line, proved the acceptable cytotoxic potency of this series. Compound 7 with IC50 = 1 μg/mL was the most active derivative. This compound showed higher activity in comparison with doxorubicin as reference drug. Molecular docking of these compounds as ligand into the active site of c-Src tyrosine kinase demonstrated the high potency for inhibition of the related enzyme. Compound 7 with binding free energy equal to -10.19 KCal/mol and five hydrogen bonds was the most potent inhibitor in comparison with other ligands.

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